Carbamoylated azithromycin incorporated zirconia hybrid monolith for enantioseparation of acidic chiral drugs using non-aqueous capillary electrochromatography

- A carbamoylated azithromycin-incorporated zirconia hybrid monolithic (AZI-ZHM) capillary column was prepared.
- The AZI-ZHM column was used for enantioseparation of acidic chiral drugs by CEC.
- Optimal conditions for chiral separations on the AZI-ZHM were investigated.

Carbamoylated derivatives of two antibiotics, namely, clindamycin phosphate (CLIP) and erythromycin (ERY) were successfully employed as co-precursors, in combination of zirconium tetrabutoxide as a precursor, to prepare chiral organic-zirconia hybrid monoliths (i.e., CLIP-ZHMs and ERY-ZHMs, respectively) via a single-step in-situ sol-gel approach in our previous works. Their superiority over chiral organic-zirconia/silica monoliths, prepared by post-modification approach, in terms of better enantioresolution and enhanced stability inspired us to prepare ZHMs based on an another antibiotic, azithromycin (i.e., AZI-ZHMs). Monolithic columns were employed for capillary electrochromatographic enantioseparation of acidic chiral drugs in mobile phases consisting of acetonitrile (ACN) and methanol (MeOH) as organic modifiers, and acetic acid (AcOH) and triethylamine (TEA) as electrolytes. The effects of composition of mobile phase and applied voltage on chiral separation were investigated by using ketoprofen as a representative analyte. Baseline resolutions were obtained for six acidic drugs in mobile phase consisting of 80/20 (v/v) ACN/MeOH with 300 mM AcOH and 10 mM TEA at a 10 kV applied voltage and 25 °C capillary temperature. The relative standard deviations for resolution values regarding column to column and batch to batch repeatability were less than 2.5% (for n = 3) under optimized conditions, indicating satisfactory stability of the columns and reproducibility of the column preparation process.